The eviQ Medical Oncology Committee recommends a more rapid infusion of bevacizumab than recommended in the product monograph, as many studies which support a more rapid infusion time of bevacizumab are now available.
The bevacizumab administration schedule recommended in the product monograph uses a 90-minute infusion with the first dose, 60-minutes with the second dose and 30-minutes with subsequent doses. However, it has been reported that a 10-minute infusion for both the 5 mg/kg dose (0.5 mg/kg per minute) and 7.5 mg/kg dose (0.75 mg/kg/min) and a 20-minute infusion for the 10 mg/kg dose (0.5 mg/kg/min)r is safe with very minimal risk of infusion reactions. In view of the published data detailed below, this more rapid rate of infusion does not appear to increase the incidence of reactions which remain extremely low, and usually mild.
First dose still should be administered over 90 minutes as per product monograph.
There is no need for standard premedication regimen for prevention or prophylaxis of infusion reactions.
Evidence in support of more rapid bevacizumab infusion
Reidy et al reported on the results of 1,077 patients who had received a total of 10,606 doses of bevacizumab over a period of 2 years between February 2004 and June 2006. 8,494 administered doses were at a dose of 5 mg/kg. No hypersensitivity reactions occurred in the first 202 patients who received 90, 60 then 30 minute infusion times. The rate was then modified to 30 minutes for all infusions with no hypersensitivity reactions. The following 2,311 doses were administered at a rate of 5 mg/kg over 10 minutes (0.5 mg/kg/min), six patients (1.6%) experienced minor clinical events consistent with hypersensitivity reactions that were not serious. The data from this trial strongly suggests that the current standard practice, as cited in the product information, of prolongation of the initial doses of bevacizumab to 90 and 60 minutes is unnecessary. This standardised rate of 0.5 mg/kg/min was safe, logical and became the adopted policy at their institution.r
Dohn et al commented on the feasibility and safety of a short infusion time of bevacizumab in combination with a fluorouracil based chemotherapy as first-line therapy for patients with metastatic colorectal cancer. Bevacizumab 5 mg/kg was administered on day 1 every 2 weeks in combination with FOLFIRI as a 10 minute intravenous infusion OR 7.5 mg/kg was given with CapeOx (XELOX protocol on eviQ) on day 1 every 3 weeks. No significant infusion problems were experienced when bevacizumab was infused over 10 minutes. Therefore it was concluded that a short infusion time of bevacizumab given in 10 minutes is feasible and well tolerated.r
Similarly, Mahfoud et al reported on the results of a study which compared the safety of bevacizumab 5 mg/kg or 7.5 mg/kg infused over different times in patients with metastatic colorectal cancer. From January 2006 to December 2008, 38 group A patients were given bevacizumab over the standard 90, 60, 30 minute infusion sequence. From January 2009, 43 patients in group B were given bevacizumab over 10 minutes. A total of 459 and 527 doses were given in group A and B respectively. No hypersensitivity reactions occurred in group A however in group B two easily resolvable events were observed in the 7.5 mg/kg group. According to these findings, it is recommended that bevacizumab 5 mg/kg or 7.5 mg/kg in metastatic colorectal cancer can be infused safely over 10 minutes.r
Mir et al evaluated the impact of a shortened infusion time of bevacizumab over 10 minutes on toxicity in non-small cell lung cancer (NSCLC) patients. 55 group A patients were given bevacizumab 7.5 mg/kg over 10 minutes every 3 weeks and 36 group B patients received the same regimen according to the standard 90, 60, 30 minute sequence. A total of 370 and 399 doses of bevacizumab were given in group A and B respectively. This study found that bevacizumab 5 mg/kg given at an infusion rate of 0.5 mg/kg/min did not increase short and/or long term reno-vascular toxicity in colorectal cancer patients. Furthermore, bevacizumab 7.5 mg/kg given over 10 minutes (infusion rate 0.75 mg/kg/min) was safe in NSCLC patients and did not result in significant toxicities regarding hypersensitivity reactions, hypertension and proteinuria.r